Chloride intracellular channel (CLIC) is a family of proteins encoded by six different genes (CLIC1-6)^1-3.

The localization of the various CLIC channels remains elusive and controversial since they can be either found in a soluble form in the cytoplasm or as integral membrane proteins (in intracellular compartments such as the nuclear membrane or the endoplasmic reticulum for example, or associated with the plasma membrane) via their single transmembrane domain¹.

When membrane associated, CLIC channels indeed function as ion channels (enabling the passage of Cl^- ions). Non-channel functions are also attributed to CLICs and include cell cycle regulation, cell differentiation, and apoptosis. These different roles depend on whether CLICs are membrane bound or cytosolic¹. For instance, CLIC4 is involved in keratinocyte differentiation in a TGFb-dependent manner^4,5, in such a way that TGFb stimulation induces the expression and nuclear localization of CLIC4 and its subsequent interaction with transcription factors⁴. CLIC4 is also required for growth arrest and apoptosis under stress⁶.

CLIC4 distribution is rather ubiquitous but shows higher expression level in the skin, kidney, brain and testes⁷.